The Ca²⁺ release-activated Ca²⁺ (CRAC) channel is a highly Ca²⁺-selective store-operated channel expressed in T cells, mast cells, and various other tissues. CRAC channels regulate critical cellular processes such as gene expression, motility, and the secretion of inflammatory mediators. The identification of Orai1, a key subunit of the CRAC channel pore, and STIM1, the endoplasmic reticulum (ER) Ca²⁺ sensor, have provided the tools to illuminate the mechanisms of regulation and the pore properties of CRAC channels. Opening of CRAC channels enables the refilling of ER Ca²⁺ stores and sustains long-lasting Ca²⁺ oscillations and plateau signals, critical for the proliferation of T cells and production of cytokines following antigenic stimulation.